Biological sensors are used in many areas of human life. The largest problem is one of portability and ease of use. One area of biosensor involves the interaction between an antibody and antigen; however, detection of the binding events when the antibody/antigen pair binds together is difficult due to a lack of electron transfer and the nature of the weak electrostatic forces involved. This drives a need for new transduction methods for the detection of these types of biological reactions.
The term, “biomolecule-binding pairs,” means that specific binding will occur between a first member and a second member of a binding pair under defined conditions of ionic strength, temperature, pH and the like. The interaction may occur due to specific electrostatic, hydrophobic, or other interaction of certain residues of the first member with specific residues of the second member to form a stable complex under conditions effective to promote the interaction.
Examples of biomolecule-binding pairs include, protein-protein interactions, protein-nucleic acid interactions, protein-small molecule interactions, nucleic acid-nucleic acid interactions, protein-fatty acid interactions, and protein-lipid interactions. A protein member of a binding pair may be an antigen, antibody, enzyme, hormone, receptor, regulatory protein, membrane protein, glycoprotein, proteoglycan, or a binding fragment, domain, or derivative of any of such proteins. A nucleic acid member of a binding pair may be deoxyribonucleic acid, or ribonucleic acid, binding fragment, domain or derivative of any of such nucleic acids. A member of a binding pair may also be a small molecule, or a substrate, for example.
There are many biosensors that are based on optical techniques. These include surface plasmon resonance (SPR), laser induced fluorescence, and radiolabeling (Huang, et al, “Prostate-specific antigen immunosensing based on mixed self-assembled monolayers, camel antibodies and colloidal gold enhanced sandwich assays,” Biosensors and Bioelectronics 21 (2005) 483-490; Armbruster, D. A., 1993, Prostate-specific antigen; biochemistry, analytical methods, and clinical application, Clin. Chem. 39, 181-195; Cattini, R., Cooksey, M., Robinson, D., Brett, G., Bacarese-Hamilton, T., Jolley, N., 1993, Measurement of alpha-fetoprotein, carcinoembryonic antigen and prostate-specific antigen in serum and heparinised plasma by enzyme immunoassay on the fully automated sereno SR1 analyzer, Eur. J. Clin. Chem. Clin. Biochem. 31, 517-524; Thompson, M., Stone, D. C., 1997; Surface-Launched Acoustic Wave Sensors; Chemical Sensing and Thin-Film Characterization, John Wiley & Sons, New York; Stenberg, E., Persson, B., Roos, H., Urbaniczky, C., 1991, Quantitative determination of surface plasmon resonance using radiolabeled proteins, J. Colloid Interface Sci. 143, 513-526).
SPR detects a change in reflected light caused by the bound biological pair on the surface. Usually, SPR is not portable due to sophisticated support electronics that are sensitive to placement and vibration. Fluorescence based methods require extensive modification of the target molecules that allow them to fluoresce light. These methods require that a fluorescent tag is able to be placed onto the target. This also requires intense laser-based excitation of the fluorophor to reach low detection limits. All of the optical techniques require large, complicated electronics to take the measurements. They can be made small enough to be called “bench top,” but not small enough to be handheld and portable.